tbuckley/cabot-search huggingface dataset:
Health as a Human Right: A Position Paper From the American College of Physicians
Authors: Matthew DeCamp, Lois Snyder Sulmasy, Isaac O. Opole, T. Brian Callister, Sue S. Bornstein, Eduardo Bruera, Jan K. Carney, Angelique N. Collamer, Kari L. Esbensen, Joseph J. Fins, Olivia I. Fuson, Amy K. Holbrook, Diana Jung, Ryan D. Mire, Kenneth M. Prager, Erik A. Wallace
Journal: Annals of Internal Medicine (2023)

The relationship of health to rights or human rights is complex. Although many find no right of any kind to health or health care, and others view health care as a right or human right, the American College of Physicians (ACP) instead sees health as a human right. The College, in the ACP Ethics Manual, has long noted the interrelated nature of health and human rights. Health as a human right also has implications for the social and structural determinants of health, including health care. Any rights framework is imperfect, and rights, human rights, and ethical obligations are not synonymous. Individual physicians and the profession have ethical obligations to patients, and these obligations can go beyond matters of rights. Society, too, has responsibilities-the equitable and universal access to appropriate health care is an ethical obligation of a just society. By recognizing health as a human right based in the intrinsic dignity and equality of all patients and supporting the patient-physician relationship and health systems that promote equitable access to appropriate health care, the United States can move closer to respecting, protecting, and fulfilling for all the opportunity for health.
Effect of Complementary Interventions to Redesign Care on Teamwork and Quality for Hospitalized Medical Patients
Authors: Kevin J. O’Leary, Julie K. Johnson, Mark V. Williams, Ronald Estrella, Krystal Hanrahan, Luci K. Leykum, G. Randy Smith, Jenna D. Goldstein, Jane S. Kim, Sara Thompson, Iva Terwilliger, Jing Song, Jungwha Lee, Milisa Manojlovich
Journal: Annals of Internal Medicine (2023)

Multiple challenges impede interprofessional teamwork and the provision of high-quality care to hospitalized patients.To evaluate the effect of interventions to redesign hospital care delivery on teamwork and patient outcomes.Pragmatic controlled trial. Hospitals selected 1 unit for implementation of interventions and a second to serve as a control. (ClinicalTrials.gov: NCT03745677).Medical units at 4 U.S. hospitals.Health care professionals and hospitalized medical patients.Mentored implementation of unit-based physician teams, unit nurse-physician coleadership, enhanced interprofessional rounds, unit-level performance reports, and patient engagement activities.Primary outcomes were teamwork climate among health care professionals and adverse events experienced by patients. Secondary outcomes were length of stay (LOS), 30-day readmissions, and patient experience. Difference-in-differences (DID) analyses of patient outcomes compared intervention versus control units before and after implementation of interventions.Among 155 professionals who completed pre- and postintervention surveys, the median teamwork climate score was higher after than before the intervention only for nurses (n = 77) (median score, 88.0 [IQR, 77.0 to 91.0] vs. 80.0 [IQR, 70.0 to 89.0]; P = 0.022). Among 3773 patients, a greater percentage had at least 1 adverse event after compared with before the intervention on control units (change, 1.61 percentage points [95% CI, 0.01 to 3.22 percentage points]). A similar percentage of patients had at least 1 adverse event after compared with before the intervention on intervention units (change, 0.43 percentage point [CI, -1.25 to 2.12 percentage points]). A DID analysis of adverse events did not show a significant difference in change (adjusted DID, -0.92 percentage point [CI, -2.49 to 0.64 percentage point]; P = 0.25). Similarly, there were no differences in LOS, readmissions, or patient experience.Adverse events occurred less frequently than anticipated, limiting statistical power.Despite improved teamwork climate among nurses, interventions to redesign care for hospitalized patients were not associated with improved patient outcomes.Agency for Healthcare Research and Quality.
Clinical Effectiveness of Cognitively Enhanced Tai Ji Quan Training on Global Cognition and Dual-Task Performance During Walking in Older Adults With Mild Cognitive Impairment or Self-Reported Memory Concerns
Authors: Fuzhong Li, Peter Harmer, Elizabeth Eckstrom, Kathleen Fitzgerald, Kerri Winters-Stone
Journal: Annals of Internal Medicine (2023)

Mild cognitive impairment (MCI) negatively impacts cognition and dual-task abilities. A physical-cognitive integrated treatment approach could mitigate this risk for dementia.
Oral Selective Estrogen Receptor Degrader for Advanced Breast Cancer
Authors: Yutaro Yoshitomi, Akihiko Shimomura, Chikako Shimizu
Journal: Journal of Clinical Oncology (2023)

Tolaney et al 1 published the results of the AMEERA-3 trial, a meaningful study exploring the safety and efficacy of amcenestrant in patients with estrogen receptor-positive (ER1)/human epidermal growth factor 2-negative (HER2-) advanced breast cancer.They concluded that amcenestrant did not improve progressionfree survival (PFS) compared with treatment of physician's choice (TPC) and that a numerical improvement was observed in patients with mutated ESR1.Fulvestrant has been used as a potent selective estrogen receptor degrader (SERD); however, frequent intramuscular injections are required owing to its low bioavailability and the need for high doses.Therefore, the development of a new SERD is urgently needed.Trials such as AMEERA-3 are valuable for addressing this inconvenience.
Costs of Cancer Prevention: Physical and Psychosocial Sequelae of Risk-Reducing Total Gastrectomy
Authors: Amber F. Gallanis, Lauren A. Gamble, Sarah G. Samaranayake, Rachael Lopez, Amanda Rhodes, Suraj Rajasimhan, Grace-Ann Fasaye, Olvan Juma, Maureen Connolly, Stacy Joyce, Ann Berger, Theo Heller, Andrew M. Blakely, Jonathan M. Hernandez, Jeremy L. Davis
Journal: Journal of Clinical Oncology (2023)

Risk-reducing surgery for cancer prevention in solid tumors is a pressing clinical topic because of the increasing availability of germline genetic testing. We examined the short- and long-term outcomes of risk-reducing total gastrectomy (RRTG) and its lesser-known impacts on health-related quality of life (QOL) in individuals with hereditary diffuse gastric cancer syndrome.
A randomized, clinical trial investigating the use of a digital intervention to reduce delirium-associated agitation
Authors: Michelle Nicholas, Jessica Wittmann, Monica Norena, Marlena Ornowska, Steven Reynolds
Journal: npj Digital Medicine (2023)

Abstract We aimed to determine if a novel digital therapeutic intervention could reduce agitation and unscheduled medication use in an adult delirious acute care population. Delirious participants were randomly allocated (1:1) to receive standard of care plus a single 4-hour exposure to the digital intervention “MindfulGarden”, which uses a screen-based delivery to display a nature landscape with dynamic adjustment of screen content in response to movement and sound or standard of care only. Between March 2021 and January 2022, 73 participants were enrolled with 70 completing the trial protocol and included in the final analysis with a mean age of 61 years and 68% being male (35 intervention, 35 control). Mean RASS was significantly lower across the 4-hour study period in the intervention arm 0.3 (0.85) vs 0.9 (0.93), p = 0.01. Exposure to a nature-based dynamic digital intervention showed benefits in agitation reduction.
Excess Pericardial Fat Is Related to Adverse Cardio-Mechanical Interaction in Heart Failure With Preserved Ejection Fraction
Authors: Sauyeh K. Zamani, Satyam Sarma, James P. MacNamara, Linda S. Hynan, Mark J. Haykowsky, Christopher M. Hearon, Denis Wakeham, Tiffany Brazile, Benjamin D. Levine, Vlad G. Zaha, Michael D. Nelson
Journal: Circulation (2023)
Deficiency in SLC25A15, a hypoxia-responsive gene, promotes hepatocellular carcinoma by reprogramming glutamine metabolism
Authors: Qiangnu Zhang, Teng Wei, Wen Jin, Lesen Yan, Lulin Shi, Siqi Zhu, Yu Bai, Yuandi Zeng, Zexin Yin, Jilin Yang, Wenjian Zhang, Meilong Wu, Yusen Zhang, Gongze Peng, Stephanie Roessler, Liping Liu
Journal: Journal of Hepatology (2023)
Novel Approach to Accelerate Lung Cancer Research: Lung-MAP and the Potential of Public-Private Partnerships
Authors: Roy S. Herbst, Charles D. Blanke, Ellen V. Sigal
Journal: Clinical Cancer Research (2023)

The National Cancer Institute recently found that death rates for non-small cell lung cancer (NSCLC) have been reduced by over 6% overall in recent years. This reduction in mortality has been accompanied by an average increase in overall survival and largely credited to the therapeutic advancements for the effective treatment of NSCLC. Numerous molecular alterations have been identified in NSCLC that have enabled the development of new drugs capable of targeting these changes and efficiently kill cancerous cells. New treatments to modulate patients' immune systems have been shown to be effective in stimulating natural immune cells to have an improved anti-cancer effect. While these types of approaches to treat cancer are providing new options for patients, leadership from the Food and Drug Administration (FDA) recognized that the expansion of targeted therapy in NSCLC presented significant promise, but evaluation of the safety and efficacy of these new drugs would be slowed if new models for conducting clinical studies were not identified. Specifically, the FDA recommended that a comprehensive approach be implemented to identify the patients that are the best candidates for these, and other new treatments based upon the molecular characteristics of their tumors, and more efficiently conduct the clinical studies necessary to evaluate the safety and efficacy of new drugs. To address this growing challenge, leading lung cancer experts and stakeholders across academia, government, industry, and patient advocacy came together to design a clinical research approach that could serve as a sustainable infrastructure for new lung cancer treatments called the Lung Cancer Master Protocol.
Comparison of SP263 and 22C3 immunohistochemistry PD-L1 assays for clinical efficacy of adjuvant atezolizumab in non-small cell lung cancer: results from the randomized phase III IMpower010 trial
Authors: Caicun Zhou, Minu K Srivastava, Hao Xu, Enriqueta Felip, Heather Wakelee, Nasser Altorki, Martin Reck, Rüdiger Liersch, Anna Kryzhanivska, Satoshi Oizumi, Hiroshi Tanaka, John Hamm, Steven L McCune, Elizabeth Bennett, Barbara Gitlitz, Virginia McNally, Marcus Ballinger, Mark McCleland, Wei Zou, Meghna Das Thakur, Silvia Novello
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Tumor samples from the phase III IMpower010 study were used to compare two programmed death-ligand 1 (PD-L1) immunohistochemistry assays (VENTANA SP263 and Dako 22C3) for identification of PD-L1 patient subgroups (negative, positive, low, and high expression) and their predictive value for adjuvant atezolizumab compared with best supportive care (BSC) in resectable early-stage non-small cell lung cancer (NSCLC). Methods PD-L1 expression was assessed by the SP263 assay, which measured the percentage of tumor cells with any membranous PD-L1 staining, and the 22C3 assay, which scored the percentage of viable tumor cells showing partial or complete membranous PD-L1 staining. Results When examining the concordance at the PD-L1-positive threshold (SP263: tumor cell (TC)≥1%; 22C3: tumor proportion score (TPS)≥1%), the results were concordant between assays for 83% of the samples. Similarly, at the PD-L1–high cut-off (SP263: TC≥50%; 22C3: TPS≥50%), the results were concordant between assays for 92% of samples. The disease-free survival benefit of atezolizumab over BSC was comparable between assays for PD-L1-positive (TC≥1% by SP263: HR, 0.58 (95% CI: 0.40 to 0.85) vs TPS≥1% by 22C3: HR, 0.65 (95% CI: 0.45 to 0.95)) and PD-L1-high (TC≥50% by SP263: HR, 0.27 (95% CI: 0.14 to 0.53) vs TPS≥50% by 22C3: HR, 0.31 (95% CI: 0.16 to 0.60)) subgroups. Conclusions The SP263 and 22C3 assays showed high concordance and a comparable clinical predictive value of atezolizumab at validated PD-L1 thresholds, suggesting that both assays can identify patients with early-stage NSCLC most likely to experience benefit from adjuvant atezolizumab. Trial registration number NCT02486718 .
Mosaic chromosomal alterations in blood across ancestries using whole-genome sequencing
Authors: Yasminka A. Jakubek, Ying Zhou, Adrienne Stilp, Jason Bacon, Justin W. Wong, Zuhal Ozcan, Donna Arnett, Kathleen Barnes, Joshua C. Bis, Eric Boerwinkle, Jennifer A. Brody, April P. Carson, Daniel I. Chasman, Jiawen Chen, Michael Cho, Matthew P. Conomos, Nancy Cox, Margaret F. Doyle, Myriam Fornage, Xiuqing Guo, Sharon L. R. Kardia, Joshua P. Lewis, Ruth J. F. Loos, Xiaolong Ma, Mitchell J. Machiela, Taralynn M. Mack, Rasika A. Mathias, Braxton D. Mitchell, Josyf C. Mychaleckyj, Kari North, Nathan Pankratz, Patricia A. Peyser, Michael H. Preuss, Bruce Psaty, Laura M. Raffield, Ramachandran S. Vasan, Susan Redline, Stephen S. Rich, Jerome I. Rotter, Edwin K. Silverman, Jennifer A. Smith, Aaron P. Smith, Margaret Taub, Kent D. Taylor, Jeong Yun, Yun Li, Pinkal Desai, Alexander G. Bick, Alexander P. Reiner, Paul Scheet, Paul L. Auer
Journal: Nature Genetics (2023)

Abstract Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS , ADM17 , PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis .
Spatial communication systems across languages reflect universal action constraints
Authors: Kenny R. Coventry, Harmen B. Gudde, Holger Diessel, Jacqueline Collier, Pedro Guijarro-Fuentes, Mila Vulchanova, Valentin Vulchanov, Emanuela Todisco, Maria Reile, Merlijn Breunesse, Helen Plado, Juergen Bohnemeyer, Raed Bsili, Michela Caldano, Rositsa Dekova, Katharine Donelson, Diana Forker, Yesol Park, Lekhnath Sharma Pathak, David Peeters, Gabriella Pizzuto, Baris Serhan, Linda Apse, Florian Hesse, Linh Hoang, Phuong Hoang, Yoko Igari, Keerthana Kapiley, Tamar Haupt-Khutsishvili, Sara Kolding, Katri Priiki, Ieva Mačiukaitytė, Vaisnavi Mohite, Tiina Nahkola, Sum Yi Tsoi, Stefan Williams, Shunei Yasuda, Angelo Cangelosi, Jon Andoni Duñabeitia, Ramesh Kumar Mishra, Roberta Rocca, Jurģis Šķilters, Mikkel Wallentin, Eglė Žilinskaitė-Šinkūnienė, Ozlem Durmaz Incel
Journal: Nature Human Behaviour (2023)

Abstract The extent to which languages share properties reflecting the non-linguistic constraints of the speakers who speak them is key to the debate regarding the relationship between language and cognition. A critical case is spatial communication, where it has been argued that semantic universals should exist, if anywhere. Here, using an experimental paradigm able to separate variation within a language from variation between languages, we tested the use of spatial demonstratives—the most fundamental and frequent spatial terms across languages. In n = 874 speakers across 29 languages, we show that speakers of all tested languages use spatial demonstratives as a function of being able to reach or act on an object being referred to. In some languages, the position of the addressee is also relevant in selecting between demonstrative forms. Commonalities and differences across languages in spatial communication can be understood in terms of universal constraints on action shaping spatial language and cognition.
A systematic review and meta-analysis of the global prevalence and determinants of COVID-19 vaccine acceptance and uptake in people living with HIV
Authors: Sahabi Kabir Sulaiman, Muhammad Sale Musa, Fatimah Isma’il Tsiga-Ahmed, Abdulwahab Kabir Sulaiman, Abdulaziz Tijjani Bako
Journal: Nature Human Behaviour (2023)

People living with HIV (PLHIV) are at higher risk of poor outcomes of SARS-CoV-2 infection. Here we report the pooled prevalence of COVID-19 vaccine acceptance/uptake and determinants among this vulnerable population of PLHIV based on a systematic review and meta-analysis of studies published by 25 August 2023. Among the 54 included studies (N = 167,485 participants), 53 (N = 166,455) provided data on vaccine acceptance rate, while 27 (N = 150,926) provided uptake data. The global prevalences of COVID-19 vaccine acceptance and uptake were 67.0% and 56.6%, respectively. Acceptance and uptake rates were 86.6% and 90.1% for the European Region, 74.9% and 71.6% for the Region of the Americas, 62.3% and 78.9% for the South-East Asian Region, 64.6% and 19.3% for the Eastern Mediterranean Region, 58.0% and 35.5% for the African Region, and 57.4% and 44.0% for the Western Pacific Region. The acceptance rate increased from 65.9% in 2020 to 71.0% in 2022, and the uptake rate increased from 55.9% in 2021 to 58.1% in 2022. Men, PLHIV aged ≥40 years and those who had recently received the influenza vaccine were more likely to accept and receive the COVID-19 vaccine. Factors associated with lower uptake included Black race, other races (Latinx/Hispanic/mixed race), low education level and being unemployed. Vaccine-related factors associated with higher acceptance included belief in vaccine effectiveness, vaccine trust, perceived high susceptibility to SARS-CoV-2 infection and fear of potential COVID-19 effect in PLHIV. Sustained efforts and targeted interventions are needed to reduce regional disparities in COVID-19 vaccine uptake among PLHIV.
A temperature-responsive intravenous needle that irreversibly softens on insertion
Authors: Karen-Christian Agno, Keungmo Yang, Sang-Hyuk Byun, Subin Oh, Simok Lee, Heesoo Kim, Kyurae Kim, Sungwoo Cho, Won-Il Jeong, Jae-Woong Jeong
Journal: Nature Biomedical Engineering (2023)
An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease
Authors: Timothy J. Kendall, Maria Jimenez-Ramos, Frances Turner, Prakash Ramachandran, Jessica Minnier, Michael D. McColgan, Masood Alam, Harriet Ellis, Donald R. Dunbar, Gabriele Kohnen, Prakash Konanahalli, Karin A. Oien, Lucia Bandiera, Filippo Menolascina, Anna Juncker-Jensen, Douglas Alexander, Charlie Mayor, Indra Neil Guha, Jonathan A. Fallowfield
Journal: Nature Medicine (2023)

Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) is the commonest cause of chronic liver disease worldwide and represents an unmet precision medicine challenge. We established a retrospective national cohort of 940 histologically defined patients (55.4% men, 44.6% women; median body mass index 31.3; 32% with type 2 diabetes) covering the complete MASLD severity spectrum, and created a secure, searchable, open resource (SteatoSITE). In 668 cases and 39 controls, we generated hepatic bulk RNA sequencing data and performed differential gene expression and pathway analysis, including exploration of gender-specific differences. A web-based gene browser was also developed. We integrated histopathological assessments, transcriptomic data and 5.67 million days of time-stamped longitudinal electronic health record data to define disease-stage-specific gene expression signatures, pathogenic hepatic cell subpopulations and master regulator networks associated with adverse outcomes in MASLD. We constructed a 15-gene transcriptional risk score to predict future hepatic decompensation events (area under the receiver operating characteristic curve 0.86, 0.81 and 0.83 for 1-, 3- and 5-year risk, respectively). Additionally, thyroid hormone receptor beta regulon activity was identified as a critical suppressor of disease progression. SteatoSITE supports rational biomarker and drug development and facilitates precision medicine approaches for patients with MASLD.
E-selectin-mediated rapid NLRP3 inflammasome activation regulates S100A8/S100A9 release from neutrophils via transient gasdermin D pore formation
Authors: Monika Pruenster, Roland Immler, Jonas Roth, Tim Kuchler, Thomas Bromberger, Matteo Napoli, Katrin Nussbaumer, Ina Rohwedder, Lou Martha Wackerbarth, Chiara Piantoni, Konstantin Hennis, Diana Fink, Sebastian Kallabis, Tobias Schroll, Sergi Masgrau-Alsina, Agnes Budke, Wang Liu, Dietmar Vestweber, Christian Wahl-Schott, Johannes Roth, Felix Meissner, Markus Moser, Thomas Vogl, Veit Hornung, Petr Broz, Markus Sperandio
Journal: Nature Immunology (2023)

S100A8/S100A9 is a proinflammatory mediator released by myeloid cells during many acute and chronic inflammatory disorders. However, the precise mechanism of its release from the cytosolic compartment of neutrophils is unclear. Here, we show that E-selectin-induced rapid S100A8/S100A9 release during inflammation occurs in an NLRP3 inflammasome-dependent fashion. Mechanistically, E-selectin engagement triggers Bruton's tyrosine kinase-dependent tyrosine phosphorylation of NLRP3. Concomitant potassium efflux via the voltage-gated potassium channel KV1.3 mediates ASC oligomerization. This is followed by caspase 1 cleavage and downstream activation of pore-forming gasdermin D, enabling cytosolic release of S100A8/S100A9. Strikingly, E-selectin-mediated gasdermin D pore formation does not result in cell death but is a transient process involving activation of the ESCRT III membrane repair machinery. These data clarify molecular mechanisms of controlled S100A8/S100A9 release from neutrophils and identify the NLRP3/gasdermin D axis as a rapid and reversible activation system in neutrophils during inflammation.
Self-regulating arousal via pupil-based biofeedback
Authors: Sarah Nadine Meissner, Marc Bächinger, Sanne Kikkert, Jenny Imhof, Silvia Missura, Manuel Carro Dominguez, Nicole Wenderoth
Journal: Nature Human Behaviour (2023)

The brain's arousal state is controlled by several neuromodulatory nuclei known to substantially influence cognition and mental well-being. Here we investigate whether human participants can gain volitional control of their arousal state using a pupil-based biofeedback approach. Our approach inverts a mechanism suggested by previous literature that links activity of the locus coeruleus, one of the key regulators of central arousal and pupil dynamics. We show that pupil-based biofeedback enables participants to acquire volitional control of pupil size. Applying pupil self-regulation systematically modulates activity of the locus coeruleus and other brainstem structures involved in arousal control. Furthermore, it modulates cardiovascular measures such as heart rate, and behavioural and psychophysiological responses during an oddball task. We provide evidence that pupil-based biofeedback makes the brain's arousal system accessible to volitional control, a finding that has tremendous potential for translation to behavioural and clinical applications across various domains, including stress-related and anxiety disorders.